Fluconazole in Dextrose Injection

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Fluconazole in Dextrose Injection is a sterile solution containing Fluconazole and Dextrose. It contains NLT 90.0% and NMT 110.0% of the labeled amount of fluconazole (C₁₃H₁₂F₂N₆O).

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. • B. Test for Dextrose

Analysis: Add a few drops of the Injection (1 in 20) to 5 mL of hot alkaline cupric tartrate TS.

Acceptance criteria: A red to orange precipitate of cuprous oxide is formed.

3 ASSAY

Procedure

Buffer: 0.82 g/L of anhydrous sodium acetate in water. Adjust with 1 N acetic acid solution to a pH of 5.0.

Diluent: Methanol and Buffer (20:80) Solution A: Methanol and Buffer (5:95) Solution B: Acetonitrile and methanol (60:40) Mobile phase: See Table 1.

Table 1

System suitability solution: 0.04 mg/mL each of benzyl alcohol and USP Fluconazole RS in Diluent

Standard solution: 0.2 mg/mL of USP Fluconazole RS in Diluent

Sample solution: Nominally 0.2 mg/mL of fluconazole from Injection in Diluent

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 261 nm

Column: 4.0-mm × 10-cm; 3-µm packing L1

Flow rate: 1 mL/min

Injection volume: 100 µL

3.2 System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for benzyl alcohol and fluconazole are about 0.8 and 1.0, respectively, from the System suitability solution.]

Suitability requirements

Resolution: NLT 1.8 between benzyl alcohol and fluconazole, System suitability solution

Tailing factor: NMT 1.5 for the fluconazole peak, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fluconazole (C₁₃H₁₂F₂N₆O) in the portion of Injection taken:

Result = (r_U /r_S ) × (C_S /C_U) × 100

r_U= peak response of fluconazole from the Sample solution

r_S = peak response of fluconazole from the Standard solution

C_S = concentration of USP Fluconazole RS in the Standard solution (mg/mL)

C_U= nominal concentration of fluconazole in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

4.1 Organic Impurities Procedure 1: For Nonpolar Impurities

Buffer, Diluent, Solution A, and Solution B: Prepare as directed in the Assay.

Mobile phase: See Table 2.

Table 2

System suitability solution: 2.4 µg/mL of 1,4-benzoquinone and 20 µg/mL of USP Fluconazole RS in Diluent

Standard solution: 2 µg/mL of USP Fluconazole RS in Diluent

Sample solution: Nominally 1.0 mg/mL of fluconazole from Injection in Diluent

4.1.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 261 nm

Column: 4.0-mm × 10-cm; 3-µm packing L1

Flow rate: 1 mL/min

Injection volume: 100 µL

4.1.2 System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for 1,4-benzoquinone and fluconazole are about 0.5 and 1.0, respectively, System suitability solution.]

Suitability requirements

Resolution: NLT 5.0 between 1,4-benzoquinone and fluconazole, System suitability solution

Tailing factor: NMT 1.5 for the fluconazole peak, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

4.1.3 Analysis

Samples: Standard solution and Sample solution

[Note—For the following calculations, do not include peaks eluting before fluconazole and do not include impurities at relative retention times of 2.00–2.12 and 3.14–3.26. The disregarded impurities at the specified relative retention times are process impurities monitored in the drug substance. Furthermore, disregard any peak due to an excipient or any peak less than 0.02%. This test is for determination of the late-eluting peaks, and hence the early-eluting peaks are not quantitated using this procedure.]

Calculate the percentage of the largest unknown nonpolar impurity in the portion of Injection taken:

Result = (r_U /r_S ) × (C_S /C_U) × 100

r_U = peak response of the largest unknown nonpolar impurity from the Sample solution

r_S = peak response of fluconazole from the Standard solution

C_S = concentration of USP Fluconazole RS in the Standard solution (mg/mL)

C_U = nominal concentration of fluconazole in the Sample solution (mg/mL)

Calculate the percentage of total unknown nonpolar impurities in the portion of Injection taken:

Result = (r_T /r_S ) × (C_S /C_U ) × 100

r_T = sum of the peak responses of all the unknown impurities from the Sample solution

r_S = peak response of fluconazole from the Standard solution

C_S = concentration of USP Fluconazole RS in the Standard solution (mg/mL)

C_U = nominal concentration of fluconazole in the Sample solution (mg/mL)

Acceptance criteria

Largest unknown nonpolar impurity: NMT 0.1%

Total unknown nonpolar impurities: NMT 0.5%

4.2 Organic Impurities Procedure 2: For Polar Impurities

Buffer, Diluent, Solution A, Solution B, Mobile phase, System suitability solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 2 µg/mL of USP Fluconazole RS in Diluent

Sample solution: Nominally 0.2 mg/mL of fluconazole from Injection in Diluent

4.2.1 System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for benzyl alcohol and fluconazole are about 0.8 and 1.0, respectively, System suitability solution.]

Suitability requirements

Resolution: NLT 1.8 between benzyl alcohol and fluconazole, System suitability solution

Tailing factor: NMT 1.5 for the fluconazole peak, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

4.2.2 Analysis

Samples: Standard solution and Sample solution

[Note—The relative retention times are listed in Table 3.]

Calculate the percentage of the single largest unknown polar impurity in the portion of Injection taken:

Result = (r_U /r_S ) × (C_S /C_U) × 100

r_U = peak response of the largest unknown polar impurity from the Sample solution

r_S = peak response of fluconazole from the Standard solution

C_S = concentration of USP Fluconazole RS in the Standard solution (mg/mL)

C_U = nominal concentration of fluconazole in the Sample solution (mg/mL)

Calculate the percentage of total unknown polar impurities in the portion of Injection taken:

Result = (r_T /r_S ) × (C_S /C_S ) × 100

r_T = sum of the peak responses of all the unknown polar impurities from the Sample solution

r_S = peak response of fluconazole from the Standard solution

C_S = concentration of USP Fluconazole RS in the Standard solution (mg/mL)

C_S = nominal concentration of fluconazole in the Sample solution (mg/mL)

Acceptance criteria: See Table 3. Disregard any peak due to an excipient or any peak less than 0.03%.

Table 3

a 5-Hydroxymethylfurfural.

b These are process impurities which are included in this table for identification only. These impurities are controlled in the drug substance. They are not to be reported for the drug product and are not included in the total impurities.

c 4-Amino-1-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-4H-1,2,4-triazolium bromide.

d 2-(2,4-Difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-3-(4H-1,2,4-triazol-4-yl)propan-2-ol.

e 2-(2,4-Difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)propane-1,2-diol.

f Potential impurity associated with drug product packaged in bags.

5 SPECIFIC TESTS

Sterility Tests 〈71〉: Meets the requirements

Bacterial Endotoxins Test 〈85〉: NMT 0.416 USP Endotoxin Units/mg of fluconazole

Other Requirements: Meets the requirements in Injections and Implanted Drug Products 〈1〉

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Fluconazole RS.